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Postmenopausal women have a higher prevalence of cataracts than men of a similar age. This study aimed to evaluate the effects of menopausal hormone therapy (MHT) on lens opacities in postmenopausal women.This retrospective cohort study analysed population-based health insurance data in South Korea collected from 2002 to 2019. To determine the risk factors associated with cataract, postmenopausal women (N = 2,506,271) were grouped according to post-MHT use. The treatment group was further divided into the following subgroups: tibolone, combined oestrogen plus progestin by manufacturer, oral oestrogen, combined oestrogen plus progestin by physician and topical oestrogen groups. The main outcome measure was the prevalence of cataracts.The control group comprised 463,151 postmenopausal women who had never used MHT after menopause, while the treatment group included 228,033 postmenopausal women who had used MHT continuously for at least 6 months. The treatment group had a higher incidence of cataracts than the control group based on Cox proportional hazards ratio analysis. Low socioeconomic status and high parity were identified as risk factors for cataracts, and reduced risk of cataracts was associated with living in rural areas and drinking alcohol.Women undergoing post-MHT, including tibolone, had a higher incidence of cataracts. Cataract development should be a concern when examining postmenopausal patients using MHT.

To survive, animals must convert sensory information into appropriate behaviours1,2. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses3–5. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs)6,7 into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly’s directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

Background/Aims: A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028.Methods: Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC.Results: The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P

Patients with interstitial lung disease (ILD) may have a poor prognosis after lung cancer surgery because of respiratory complications and increased recurrence rates due to limited resection. Few studies have investigated prognosis after surgery by matching clinical variables between patients with and without ILD.Medical records of patients who underwent lung cancer surgery between January 2010 and August 2020 at a referral hospital in South Korea were reviewed. Patients with ILD were identified based on preoperative computed tomography findings. Through propensity score matching, the clinical outcomes and prognoses of patients with (ILD group) and without ILD (control group) were compared.Of 1629 patients, 113 (6.9%) patients with ILD were identified, of whom 104 patients were matched. Before matching, patients with ILD had higher mean age, proportion of men, and rates of sublobar resection and squamous cell carcinoma than those without ILD. After matching, there was no significant difference in postoperative mortality rates between the control and ILD groups. The 5-year survival rate was significantly lower in the ILD group (66%) than in the control group (78.8%; P= .007). The 5-year survival rate of the ILD-GAP (Gender, Age, Physiology) stage III group (12.6%) was significantly lower than that of the ILD-GAP stage I (73.5%) and II groups (72.6%; P.0001). Multivariable Cox analysis demonstrated that idiopathic pulmonary fibrosis, higher clinical stage, and recurrence were independent prognostic factors for mortality.Concomitant ILD negatively affects long-term prognosis after lung cancer surgery, and ILD subtype and physiological severity assessment help predict prognosis after surgery.

Background/Aims: We evaluated the gut microbiome using extracellular vesicles (EVs) in the urine of patients with colorectal cancer (CRC) to determine whether gut-microbe-derived EVs could be a potential biomarker for the diagnosis of CRC.Methods: EVs were isolated from the urine of patients with CRC and healthy controls. DNA was extracted from the EVs, and the bacterial composition was analyzed using next-generation sequencing of the 16S rRNA.Results: A total of 91 patients with CRC and 116 healthy controls were enrolled. We found some specific microbiomes that were more or less abundant in the CRC group than in the control group. The alpha-diversity of the gut microbiome was significantly lower in the CRC group than in the control group. A significant difference was observed in the beta-diversity between the groups. The alpha-diversity indices between patients with early- and late-stage CRC showed conflicting results; however, there was no significant difference in the beta-diversity according to the stage of CRC. There was no difference in the alpha- and beta-diversity of the gut microbiome corresponding to the location of CRC (proximal vs. distal).Conclusions: A distinct gut microbiome is reflected in the urine EVs of patients with CRC compared with that in the healthy controls. Microbial signatures from EVs in urine could serve as potential biomarkers for the diagnosis of CRC.

The prevalence of dementia and aortic stenosis (AS) increases with each decade of age. Transcatheter aortic valve replacement (TAVR) is a definitive treatment for AS, but there are scarce data on morbidity, mortality, and readmission risk after TAVR in patients with dementia.We identified all admissions for TAVR in patients with AS in the National Readmissions Database in 2017-2018 and stratified them according to the presence or absence of a secondary diagnosis of dementia. Inpatient outcomes were compared using logistic regression. Cox proportional-hazards models were used to compare 30-, 60-, and 90-day readmissions.A total of 48,923 index hospitalizations for TAVR were identified, of which 2192 (4.5 %) had a secondary diagnosis of dementia. Presence of dementia was associated with higher odds of delirium, pacemaker placement, acute kidney injury, and fall in hospital. The hazard of 30-day readmission was not significantly different between patients with and without dementia, but patients with dementia experienced a higher hazard of 60-day readmission (HR 1.15, 95 % CI 1.03-1.26, p = 0.011) in the unadjusted model and higher hazard of 90-day readmission in both unadjusted (HR 1.18, 95 % CI 1.08-1.30, p0.001) and adjusted models (aHR 1.14, 95 % CI 1.04-1.25, p = 0.004).Patients with dementia who undergo TAVR are at higher risk of in-hospital adverse outcomes and 60- and 90-day readmissions compared with patients without dementia. These estimates should be integrated into shared decision-making discussions with patients and families.

The superiority of angiotensin receptor-neprilysin inhibitor (ARNI) over angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) has not been reassessed after the publication of recent trials that did not find clinical benefits. Therefore, we performed an updated network meta-analysis comparing the efficacy and safety of ARNI, ACE-I, ARB, and placebo in heart failure with reduced ejection fraction. We included randomized clinical trials that compared ARNI, ARB, ACE-I, and placebo in heart failure with reduced ejection fraction. We extracted prespecified efficacy end points and produced network estimates, p scores, and surface under the cumulative ranking curve scores using frequentist and Bayesian network meta-analysis approaches. A total of 28 randomized controlled trials including 47,407 patients were included. ARNI was associated with lower risk of all-cause mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68 to 0.96), cardiac death (RR 0.79, 95% CI 0.64 to 0.99), and major adverse cardiac events (MACEs; RR 0.83, 95% CI 0.72 to 0.97) but higher risk of hypotension (RR 1.46, 95% CI 1.02 to 2.10) than ARB. ARNI was associated with lower risk of MACE (RR 0.85, 95% CI 0.74 to 0.97), but higher risk of hypotension (RR 1.69, 95% CI 1.27 to 2.24) compared with ACE-I. P scores and surface under the cumulative ranking curve scores demonstrated superiority of ARNI over ARB and ACE-I in all-cause mortality, cardiac death, MACE, and hospitalization for heart failure. In conclusion, ARNI was associated with improved clinical outcomes, except for higher risk of hypotension, compared with ARB and ACE-I.

This study aimed to explore the possibility and clinical utility of existing artificial intelligence (AI)-based computer-aided detection (CAD) of lung nodules to identify pulmonary oligometastases.The chest computed tomography (CT) scans of patients with lung metastasis from colorectal cancer between March 2006 and November 2018 were analyzed. The patients were selected from a database of 1395 patients and studied in 2 cohorts. The first cohort included 50 patients, and the CT scans of these patients were independently evaluated for lung-nodule (≥3 mm) detection by a CAD-assisted radiation oncologist (CAD-RO) as well as by an expert radiologist. Interobserver variability by 2 additional radiation oncologists and 2 thoracic surgeons were also measured. In the second cohort of 305 patients, survival outcomes were evaluated based on the number of CAD-RO-detected nodules.In the first cohort, the sensitivity and specificity of the CAD-RO for identifying oligometastatic disease (OMD) from varying criteria by ≤2 nodules, ≤3 nodules, ≤4 nodules, and ≤5 nodules were 71.9% and 88.9%, 82.9% and 93.3%, 97.1% and 73.3%, and 97.5% and 90.0%, respectively. The sensitivity of the CAD-RO in the nodule detection compared with the radiologist was 81.6%. The average (standard deviation) sensitivity in interobserver variability analysis was 80.0% (3.7%). In the second cohort, the 5-year survival rates of patients with 1, 2, 3, 4, or ≥5 metastatic nodules were 75.2%, 52.9%, 45.7%, 29.1%, and 22.7%, respectively.Proper identification of the pulmonary OMD and the correlation between the number of CAD-RO-detected nodules and survival suggest the potential practicality of AI in OMD recognition. Developing a deep learning-based model specific to the metastatic setting, which enables a quick estimation of disease burden and identification of OMD, is underway.

The present study aimed to investigate the clinical features of patients with direction-changing spontaneous nystagmus (DCSN) and gain insight into its underlying mechanisms.Medical records and vestibular function test results collected in our dizziness clinic between February 2013 and February 2020 were retrospectively reviewed. Spontaneous nystagmus was recorded while sitting upright using videonystagmography for 2 min to confirm the spontaneous changes in nystagmus direction. Causative disease diagnoses were based on the patients' clinical history, audiometry results, vestibular function tests, and imaging studies.Of 4786 patients, DCSN was observed in 41 (0.86%). Causative disease diagnoses included vestibular neuritis (n = 9), lateral semicircular canal cupulopathy (n = 9), cerebellopontine angle tumor (n = 8), vestibular paroxysmia (n = 2), vestibular migraine (n = 2), vestibular nucleus infarction (n = 1), sudden sensorineural hearing loss with vertigo (n = 2), Meniere's disease (n = 2), Ramsay Hunt syndrome (n = 1), labyrinthine fistula due to middle ear cholesteatoma (n = 1), lateral semicircular canal dysplasia (n = 1), post tympanomastoidectomy dizziness (n = 1), and head trauma (n = 2).Although the periodicity of DCSN could not be determined because of insufficiently long observation times, it was observed in various central and peripheral vestibulopathies. Careful examination of spontaneous nystagmus over a sufficient period may ensure the detection of DCSN when evaluating dizziness.

To determine the effect of Korean medicine treatment of avascular necrosis of the femoral head (ANFH) this study reviewed both single ingredients and bioactive compounds in the treatment of ANFH in a rat model. Literature was retrieved from PubMed and Google Scholar using the keywords “femur head necrosis,” “natural extract,” and “rat.” The data from studies analyzed included: rats’ characteristics, development methods of ANFH, natural extracts administration, observation methods, and outcome indicators. Two independent researchers screened all articles retrieved and 26 studies were chosen. The most used rat species was the Sprague Dawley rat (76.9%). To induce ANFH, steroid injections (46.2%), and oral gavage (53.8%) were typically used. Studies focused mainly on factors affecting bone formation (65.3%), and apoptosis (53.8%). Research on ANFH focused on using traditional natural substances mentioned in classical literature to confirm its effectiveness against anti-inflammation, osteogenesis, and cell death. ANFH has a diverse etiology, therefore research models such as genetic analysis of human-derived samples from ANFH patients may shed more light on the condition. Moreover, research into herbal medicines and pharmacoacupuncture treatment of ANFH should precede.

We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder.The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts.For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state.The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

Since Parkinson's disease (PD) is a heterogeneous disorder with symptoms, such as tremors, gait and speech disturbances, or memory loss, individualized diagnostics are needed to optimize treatment. In their current form, the typical paper-pencil methods traditionally used to track disease progression are too coarse to capture the subtleties of clinical phenomena. For this reason, digital biomarkers that capture, for example, motor function, cognition, and behavior using apps, wearables, and tracking systems are becoming increasingly established. However, given the high prevalence of cognitive impairment in PD, digital cognitive biomarkers to predict mental progression are important in clinical practice. This pilot study aimed to identify those components of our digital version of the TMT (dTMT) that allow discrimination between PD patients with and without cognitive deficits. A total of 30 healthy control (age 66.3 ± 8.61) and 30 participants with PD (age 68.3 ± 9.66) performed the dTMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed between and inside circles. The decomposition of cognitive abilities based on integrating additional variables in the dTMT revealed that the Parkinson's disease group was significantly more sensitive to parameters of inhibitory control. In contrast, the mild cognitive impairment group was sensitive to parameters of cognitive flexibility and working memory. The dTMT allows objective, ecologically valid, and long-term cognitive and fine-motor performance tracking, suggesting its potential as a digital biomarker in neurodegenerative disorders.

This study aimed to analyze the clinicopathological prognostic factors affecting the survival of patients with oral squamous cell carcinoma (OSCC).A retrospective study was conducted on patients with OSCC who received treatment at the Oral Oncology Clinic of the National Cancer Center (NCC) from June 2001 to December 2020. The patients' sex, age, primary site, T stage, node metastasis, TNM staging, perineural invasion (PNI), lymphovascular invasion (LVI), differentiation, surgical resection margin, smoking, and drinking habits were investigated to analyze risk factors. For the univariate analysis, a Kaplan-Meier survival analysis and log-rank test were used. Additionally, for the multivariable analysis, a Cox proportional hazard model analysis was used. For both analyses, statistical significance was considered whenDuring the investigation period, 407 patients were received surgical treatment at the NCC. Their overall survival rate (OS) for five years was 70.7%, and the disease-free survival rate (DFS) was 60.6%. The multivariable analysis revealed that node metastasis, PNI, and differentiation were significantly associated with poor OS. For DFS, PNI and differentiation were associated with poor survival rates.In patients with OSCC, cervical node metastasis, PNI, and differentiation should be considered important prognostic factors for postoperative survival.

Objectives: In patients with chronic rhinosinusitis (CRS), olfactory dysfunction (OD) is a common complaint. The focus of this research was to evaluate the effectiveness of olfactory training (OT) in patients with CRS after sinonasal surgery. Design : Prospective controlled trial. Participants: We enrolled 111 Korean CRS patients who underwent sinonasal surgery. Main Outcome Measures: At baseline and three months after starting OT, both participants were assessed by an olfactory function test and endoscopy. The Korean version of the Sniffin’ stick II (KVSS-II) was used to perform the olfactory function test. A visual analog scale and the Mini-Mental State Examination were used to assess nasal and psychological functions. Over the course of three months, five odorants were used in OT (rose, lemon, cinnamon, orange, and peach). Results: Over a 12-week duration, OT increased olfactory activity in nearly 62 percent of subjects than in non-OT subjects. The OT group had significantly higher olfactory outcomes for the total KVSS-II and identification scores than the non-OT group between the initial and follow-up assessments. The initial score influenced the degree of olfactory improvement after OT. Conclusions: OT patients exhibited significantly higher total KVSS-II scores compared with non-OT patients after sinonasal surgery; in particular, the odor identification score was different between the two groups. The results of this study show that a 12-week period of repeated short-term exposure to various odors could be useful in enhancing olfactory activity in patients who underwent sinonasal surgery for the improvement of sensory-neural olfactory impairment.

Background. A combination of the reduction mammoplasty technique and breast reconstruction allows surgeons to lift ptotic breasts through local flaps and skin reduction during surgery for breast cancer. This study presents a reliable course for the combination of partial and skin or nipple-sparing mastectomy with reduction-reconstruction surgery. Methods. Fifty-seven patients underwent a partial mastectomy before reduction mammoplasty of both breasts during the same time period between 2014 and 2021 at our institution and thirteen patients underwent skin or nipple-sparing mastectomy, breast reconstruction with an extended latissimus dorsi flap or silicone implant, and aesthetic reduction mammoplasty of the contralateral breast during the same time period. Additional photos were obtained preoperatively, immediately after the operation, and at one, three, six, and twelve months postoperatively. Patient satisfaction was evaluated preoperatively and postoperatively and postoperative complications were noted. Results. Among the patients who underwent a partial mastectomy, the mean age was 45.18 ± 11.05 years, the mean body mass index (BMI) was 26.74 ± 3.53 kg/m2, and the mean preoperative right and left breast volumes were 663.85 (±28.12) cc and 664.34 (±37.13) cc, respectively, and the mean excised mass weight was 177.74 (±213.93) g. Among the patients who underwent a skin-sparing mastectomy, the mean age was 51.62 ± 8.96 years, the mean BMI was 26.91 ± 4.34 kg/m2, and the mean preoperative right and left breast volumes were 624.17 (±98.52) cc and 562.31 (±80.81) cc, respectively, and the mean excised mass weight was 618.05 (±338.17) g. Four patients (5.3%) in the partial mastectomy group had fat necrosis. The mean patient satisfaction score was higher postoperatively in both groups. Conclusion. Patients with breast cancer and large and/or ptotic breasts can successfully undergo reduction mammoplasty for both breasts immediately following partial mastectomy and nipple or skin-sparing mastectomy.

PurposeFebrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methodsWe conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). ResultsSince January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p

The liver provides a unique niche of lymphocytes enriched with a large proportion of innate-like T cells. However, the heterogeneity and functional characteristics of the hepatic T-cell population remain to be fully elucidated.We obtained liver sinusoidal mononuclear cells from the liver perfusate of healthy donors and recipients with HBV-associated chronic liver disease (CLD) during liver transplantation. We performed a CITE-seq analysis of liver sinusoidal CD45We identified a distinct CD56In summary, the current study found a distinct CD56The role of different immune cell populations in the liver is becoming an area of increasing interest. Herein, we identified a distinct T-cell population that had features similar to those of natural killer (NK) cells - a type of innate immune cell. This distinct population was expanded in the livers of patients with chronic liver disease and could thus have pathogenic relevance.

Background/Aim: The profile of patients with hepatocellular carcinoma (HCC) has changed globally; the role of etiology in predicting prognosis of HCC patients remains unclear. We aimed to analyze the characteristics and prognosis of Korean patients with HCC according to disease etiology.Methods: This retrospective observational study included patients diagnosed with HCC between 2010 and 2014 in a single center in Korea. Patients with HCC aged